Coxiella burnetii is an obligate intracellular pathogen of humans. Spore-like particles develop during bacterial infection that are highly infectious when aerosolized. Very little is known about virulence determinants produced by C. burnetii, however, a type IV secretion system associated with this pathogen is thought to deliver proteins into mammalian host cells that enable intracellular trafficking and replication of the organism. We have identified multiple C. burnetii proteins that are substrates of this type IV secretion system. In this project we will use SILAC-labeling techniques to identify mammalian proteins targeted by these C. burnetii type effectors. Biochemical, genetic and proteomic approaches will be used to determine the in vivo function of these virulence determinants.